Co-purification of a ribonuclease and human chorionic gonadotrophin beta-core protein from human urine and displacement of 125I-human luteinizing hormone from Candida albicans binding sites by ribonucleases

OBJECTIVE: To re-examine the minimal effective dose of conjugated estrogen (CEE)-progestin hormone replacement on postmenopausal bone loss. DESIGN: A 2-year, prospective, open label, randomized study. SETTING: Department of Obstetrics and Gynecology of a university hospital. PARTICIPANTS: Fifty-two postmenopausal or oophorectomized women. INTERVENTION: One of the following regimens was continuously administered for 2 years: (1) CEE 0.625 mg/day, (2) CEE 0.625 mg + medroxyprogesterone (MPA) 2.5 mg/day, (3) CEE 0.31 mg + MPA 2.5 mg/day and (4) control. MEASUREMENTS: Lumbar spine and femoral BMD by dual energy X-ray absorptiometry (DXA), a monthly based incidence of bleeding, serum lipids, PTH, calcitonin. A1-p, and osteocalcin. RESULTS: Of the 52 patients enrolled in this study, 49 patients completed the 1 year of therapy and 36 completed the 2- year study. The control group showed a significant decrease in lumbar BMD over the 2 years (P < 0.05). The % changes in lumbar BMD at 2 years of CEE alone, CEE 0.625 + MPA and CEE 0.31 + MPA were 8.52% (95% confidence intervals; 4.61 approximately 12.4%), 7.4% (0.60 approximately 14.2%) and 3.20% (0.61 approximately 5.84%), respectively, and were significantly higher than pretreatment values. The incidence of bleeding was significantly lower in women taking CEE 0.31 mg + MPA. HDL cholesterol increased in women taking CEE 0.625 mg alone or with MPA. No significant changes in lipid profiles were seen in the control or in the group of women taking CEE 0.31 mg + MPA. CONCLUSIONS: Continuous hormone replacement therapy (HRT) using 0.31 mg of CEE and 2.5 mg of MPA is effective in increasing lumbar BMD in postmenopausal or oophorectomized women and can be an appropriate option for women with a normal lipid profile or those women wishing to eliminate unscheduled bleeding.     

Effect of endothelin-1 in man--impact on basal and stimulated concentrations of luteinizing hormone, follicle-stimulating hormone, thyrotropin, growth hormone, corticotropin, and prolactin

The effect of endothelin-1 on basal and stimulated serum (plasma) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH), prolactin (PRL), growth hormone (GH), and corticotropin was investigated in healthy male volunteers (n = 5). Intravenous (IV) administration of endothelin-1 (5 ng/kg/min for 15 minutes, followed by 2.5 ng/kg/min for 105 minutes) induced an increase in basal plasma concentrations of corticotropin. Serum concentrations of PRL, TSH, LH, FSH, and GH remained unchanged. The increase in serum concentrations of these pituitary hormones induced by IV administration of LH-releasing hormone ([LH-RH] 100 micrograms), thyrotropin RH ([TRH] 400 micrograms), GH-RH (100 micrograms), and corticotropin-releasing factor ([CRF] 100 micrograms) was suppressed in regard to PRL (P < .01) and GH (P < .01) and enhanced in regard to corticotropin (P < .01). Stimulated serum concentrations of LH and FSH also tended to be higher following administration of endothelin-1 (P < .05), whereas the increase in serum concentrations of TSH remained unchanged. Thus, when administered in pharmacological doses, endothelin-1 influences pituitary hormone secretion in man.     

Hypothalamic-pituitary-ovarian response to clomiphene citrate in women with polycystic ovary syndrome

OBJECTIVE: To examine the hypothalamic-pituitary sites of clomiphene citrate (CC) action in women with polycystic ovarian syndrome (PCOS). DESIGN: Prospective controlled trial. PATIENTS, PARTICIPANTS: Seventeen women with PCOS and 9 normal-cycling women. INTERVENTIONS: Subjects with PCOS received CC, 150 mg/d for 5 days. MAIN OUTCOME MEASURES: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and LH pulse characteristics and their response to gonadotropin-releasing hormone (GnRH, 10 micrograms) were examined before and after 3 days of CC in PCOS subjects during a 12-hour frequent sampling study (n = 8). Daily urinary estrone glucuronide and pregnanediol glucuronide levels after CC were compared with concentrations in normal-cycling women through one menstrual cycle. In another nine PCOS subjects, pituitary and ovarian hormonal cyclicity was monitored by daily blood sampling. RESULTS: Thirteen of 17 treated cycles were ovulatory with normal luteal phases. In the ovulatory cycles, serum LH, FSH, estradiol (E2), and estrone levels increased after CC. Luteinizing hormone pulse frequency was unchanged, but LH pulse amplitude increased significantly after CC. Both LH and FSH response to exogenous GnRH was significantly attenuated after CC treatment. In anovulatory cycles, serum LH, FSH, and E2 increased initially and then returned to baseline and remained unchanged for the ensuring 40 days. CONCLUSIONS: Clomiphene citrate-induced ovulation in women with PCOS is accompanied by increased secretion of LH and FSH with enhanced estrogen secretion. The increased LH pulse amplitude after CC, together with decreased pituitary sensitivity to GnRH, suggests a hypothalamic effect.     

In vivo bioavailability and metabolism of topical diclofenac lotion in human volunteers

OBJECTIVE: To characterize the long-term impact of four hormone therapy regimens on insulin and glucose concentrations measured during a standard oral glucose tolerance test. RESEARCH DESIGN AND METHODS: The Postmenopausal Estrogen/Progestin Intervention Study was a 3-year placebo-controlled randomized trial to assess effects of four hormone regimens on cardiovascular risk factors. This efficacy analysis describes glucose and insulin concentrations from 788 adherent women at baseline and at 1 and 3 years' postrandomization. RESULTS: When compared with women taking placebo, those taking conjugated equine estrogen (CEE) at 0.625 mg/day with or without a progestational agent had mean fasting insulin levels that were 16.1% lower, mean fasting glucose levels 2.2 mg/dl lower, and mean 2-h glucose levels 6.4 mg/dl higher (each nominal P < 0.05). No significant differences were apparent between women taking CEE only versus the three progestin regimens: medroxyprogesterone acetate (MPA) at 2.5 mg daily (continuous MPA), MPA at 10 mg on days 1-12 (cyclical MPA), and micronized progesterone (MP) (cyclical) at 200 mg on days 1-12. The impact of hormone therapy on insulin and glucose depended on baseline levels of fasting insulin and 1-h glucose (P < 0.05). However, the treatment effects on carbohydrate metabolism appeared to be consistent across participant subgroups formed by lifestyle, clinical, and demographic characteristics. CONCLUSIONS: Oral hormone therapy involving 0.625 mg/day of CEE may modestly decrease fasting levels of insulin and glucose. Postchallenge glucose concentrations are increased, however, which may indicate delayed glucose clearance.     

Effects of growth hormone, prolactin, insulin-like growth factors, and gonadotropins on progesterone secretion by porcine luteal cells

Growth hormone (GH) and IGF-I have receptors within the corpus luteum (CL) and stimulate CL function. Our objective was to investigate the effects of GH, prolactin (PRL), IGF-I, IGF-II, LH, and FSH on progesterone secretion by porcine luteal cells during mid-pregnancy. Gilts (crossbred Yorkshire/Landrace) were slaughtered on d 44 of pregnancy and CL were collected. Large and small luteal cells (LLC and SLC, respectively) were obtained from dissociated CL and separated by elutriation. Luteal cells were incubated with 0, 1, 10, or 100 ng/mL of GH, PRL, IGF-I, IGF-II, LH, and FSH or combinations of 10 ng/mL of these reagents for 24 or 48 h. Culture media were harvested and concentrations of progesterone analyzed by radioimmunoassay. Growth hormone, PRL, and IGF-I increased (P < .05; 100 ng/mL dose) concentrations of progesterone in media of LLC. Insulin-like growth factor-II, LH, and FSH had no effect on progesterone in LLC cultures. In SLC cultures, GH, PRL, IGF-I, IGF-II, and FSH failed to stimulate progesterone secretion, whereas LH increased progesterone secretion (linear effect of dose; P < .05). Combinations (10 ng/mL each hormone) of GH and IGF-I or PRL and IGF-I increased progesterone secretion by LLC compared with control, GH, PRL, or IGF-I alone (P < .05). Similar combinations of GH or PRL with IGF-I had no effect on SLC. Conclusions are that GH and PRL are stimulatory to progesterone secretion by LLC (location of GH receptor) and SLC are responsive to LH during mid-pregnancy. Both GH and PRL are synergistic with IGF-I for increased progesterone secretion.     

Ovarian recovery after total body irradiation and allogeneic bone marrow transplantation: long-term follow up of 79 females

Seventy-nine females undergoing allogeneic BMT following conditioning with total body irradiation (TBI), were prospectively followed between March 1983 and March 1992 with regular gynaecological examinations, including plasma levels of luteinising hormone (LH), follicle stimulating hormone (FSH), 17-beta oestradiol (E2) and pelvic ultrasonography. The end-points of this study were the following: (1) early and late effects of TBI on ovarian function, (2) compliance and results of hormonal replacement therapy (HRT), and (3) predictive events for ovarian recovery. During the first year post-BMT most adult women complained of vasomotor and/or genitourinary tract symptoms. These were associated with decreased E2 and increased LH-FSH plasma levels and a deterioration in their sexual life (94% of sexually active women). Forty-nine adult females were selected to receive systemic hormonal replacement therapy (HRT), consisting of cyclic transdermal oestrogens plus medroxyprogesterone acetate (MPA) or cyclic oral therapy with low doses of conjugated oestrogens and MPA: these patients were selected on the basis of age (< 45 years), absence of medical contraindications or subjective refusal. Compliance and tolerability were overall good: most women (65%) never stopped HRT; this was discontinued in 14 patients for medical reasons and in 3 because of refusal. Forty-three females completed 6 months of HRT: vasomotor symptoms disappeared in 91% of 58 women who previously referred these symptoms. Improvement of genitourinary symptoms was seen both with local and systemic hormonal therapy. However sexual symptoms were reduced in 21 of 26 women (81%) given HRT compared with 8 of 19 (42%) women given local treatment (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis

Although estrogen replacement therapy is associated with reduced risk of coronary heart disease and reduced extent of coronary artery atherosclerosis, the effects of combined (estrogen plus progestin) hormone-replacement therapy are uncertain. Some observational data indicate that users of combined hormone replacement consisting of continuously administered oral conjugated equine estrogens (CEE) and oral sequentially administered (7 to 14 days per month) medroxyprogesterone acetate (MPA) experience a reduction in risk similar to that of users of CEE alone. However, the effects of combined, continuously administered CEE plus MPA (a prescribing pattern that has gained favor) on the risk of coronary heart disease or atherosclerosis are not known. We studied the effects of CEE (monkey equivalent of 0.625 mg/d) and MPA (monkey equivalent of 2.5 mg/d), administered separately or in combination, on the extent of coronary artery atherosclerosis (average plaque size) in surgically postmenopausal cynomolgus monkeys fed atherogenic diets and treated with these hormones for 30 months. Treatment with CEE alone resulted in atherosclerosis extent that was reduced 72% relative to untreated (estrogen-deficient) controls (P < .004). Atherosclerosis extent in animals treated with CEE plus MPA or MPA alone did not differ from that of untreated controls. Although treatment had marked effects on plasma lipoprotein patterns, statistical adjustment for variation in plasma lipoproteins did not alter the between-group relationships in atherosclerotic plaque size, suggesting that these factors do not explain substantially the atheroprotective effect of estrogen or the MPA-associated antagonism. Although the mechanism(s) remains unclear, we conclude that oral CEE inhibits the initiation and progression of coronary artery atherosclerosis and that continuously administered oral MPA antagonizes this atheroprotective effect.     

Follicle stimulating hormone alone supports follicle growth and oocyte development in gonadotrophin-releasing hormone antagonist-treated monkeys

Both follicle stimulating hormone (FSH) and luteinizing hormone (LH) are proposed requirements for follicular growth and steroidogenesis; however, the role of LH in primate folliculogenesis is unclear. Follicular stimulation by recombinant human FSH (n = 5) with and without recombinant LH (1:1; n = 6) following 90 days of gonadotrophin-releasing hormone (GnRH) antagonist (Antide) treatment in macaques was evaluated. Human chorionic gonadotrophin (HCG) was administered when six follicles > or = 4 mm were observed. Oocytes were aspirated 27 h later and inseminated in vitro. Chronic Antide reduced serum oestradiol and bioactive LH to concentrations observed in hypophysectomized rhesus monkeys. Multiple follicular growth required a longer interval following recombinant FSH (12 +/- 1 days) than recombinant FSH+recombinant LH (9 +/- 0.2 days), but the total number of follicles/animal did not differ between groups. The day prior to HCG, oestradiol concentrations were 4-fold less following recombinant FSH compared to recombinant FSH+recombinant LH. With recombinant FSH, more oocytes completed meiosis to metaphase II (51%) and fertilized (89 +/- 5%) relative to recombinant FSH+recombinant LH (12 and 52 +/- 11% respectively). Follicular growth and maturation in LH-deficient macaques occurred with FSH alone. Thus, LH is not required for folliculogenesis in primates. Higher fertilization rates following follicular stimulation with FSH alone suggest that the presence of LH with FSH (1:1) during the pre-ovulatory interval impairs gametogenic events in the periovulatory period.     

Serum sex hormones are altered in patients with chronic temporal lobe epilepsy receiving anticonvulsant medication

PURPOSE: To evaluate the changes in serum sex hormones of gonadal or adrenal origin, the gonadotropic hormones, and sex hormone-binding globulin (SHBG) in men and women with chronic temporal lobe epilepsy (TLE), who are undergoing monotherapy with carbamazepine or receiving carbamazepine in combination with other anticonvulsant drugs. METHODS: Gonadal hormones (estradiol, testosterone, free testosterone, and inhibin B), adrenal hormones [cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and 17alpha-hydroxyprogesterone], and gonadotropic hormones (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) were measured in 22 women and 26 men with TLE. The study also measured prolactin; human growth hormone and its major mediator, insulin-like growth factor-I; thyroid hormones (free thyroxine and free triiodothyronine); thyroid-stimulating hormone (TSH); and SHBG. The results were compared with those obtained from 60 healthy women and 106 healthy men. RESULTS: In the female patients, TSH, DHEAS, follicular-phase LH, and luteal-phase estradiol were significantly lower than in the control groups, with prolactin and SHBG significantly higher. In the male patients, DHEAS, 17alpha-hydroxyprogesterone, free testosterone, inhibin B, and the testosterone/LH ratio were significantly lower than in the control group, with LH, FSH, and SHBG significantly higher. Increased FSH in 31% of the men indicates an impairment of spermatogenesis; lowered inhibin B in 12% indicates an impaired Sertoli's cell function; and the decreased testosterone/LH ratio in 50% indicates an impaired Leydig's cell function. CONCLUSIONS: The case patients had endocrine disorders, mainly concerning the gonadotropic and gonadal functions in both sexes; the adrenal function, with lowered DHEAS levels in both sexes; and lowered 17alpha-hydroxyprogesterone levels in the men. SHBG levels were increased in patients taking anticonvulsant medications.     

Changing estrogen and progesterone receptor patterns in breast carcinoma during the menstrual cycle and menopause

BACKGROUND: Estrogen receptor (ER) and progesterone receptor (PgR) status at the time of breast carcinoma surgery is used as a marker of both prognosis and hormone dependency to guide adjuvant therapy. The authors studied the influence of hormonal milieu at the time of surgery on ER and PgR levels. METHODS: A population of 2020 patients with breast carcinoma, including 575 premenopausal women, was analyzed. ER and PgR levels were determined by radioligand binding assays (cutoff values, 10 fmol/mg). Serum estradiol (E2), progesterone (Pg), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels obtained on the day of surgery were used to define the menstrual cycle phase in premenopause. RESULTS: In premenopause, there was a higher proportion of ER positive (ER+) tumors in the follicular phase (62%, n = 316) than in the ovulatory phase (51%, n = 59) and the luteal phase (53%, n = 200, P = 0.03). The mean ER level was also higher in the follicular phase (30 fmol/mg) than in the ovulatory phase (20 fmol/ mg) and the luteal phase (25 fmol/mg, P < 0.001). The percentage of PgR positive (PgR+) tumors tended to be higher in the ovulatory phase (85%) than in the follicular (78%) and luteal (72%) phases (P = 0.11). The mean PgR was also higher in the ovulatory phase (177 fmol/mg) than in the follicular and luteal phases (134 and 92 fmol/mg, respectively; P < 0.001). The percentage of ER+ tumors was higher among menopausal women than among premenopausal women (67% vs. 59%, respectively; P < 0.001). Conversely, the percentage of PgR+ tumors was lower among menopausal women than among premenopausal women (65% vs. 78%, respectively; P < 0.001). In premenopause, there was a weak negative correlation between ER and E2 levels. No correlations were found between levels of ER and Pg and levels of FSH and LH or among levels of PgR and E2, Pg, and FSH and LH in premenopausal and menopausal women. CONCLUSIONS: Changes in ER and PgR levels in breast carcinoma during the menstrual cycle and menopause suggest that interpretations of hormone dependency on the basis of steroid receptor values should take into account hormonal status at the time of surgery.     

The effect of LHRH and TRH on human interferon-gamma production in vivo and in vitro

Accumulating evidence suggests that hypothalamic luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) are two hypophysiotropic factors which modulate the immune response. The aim of the present study was to determine the in vivo effects of an intravenous bolus of LHRH and TRH on plasma interferon (IFN)-gamma production in five normoprolactinemic women with irregular menstrual cycles. We also determined prolactin (PRL), thyrotropin (TSH), follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels before and after intravenous administration of LHRH and TRH. The results demonstrate that intravenous bolus of LHRH/TRH increases plasma IFN-gamma levels, with the maximum response 45 min after in vivo administration of hypothalamic peptides and after peak levels of adenohypophyseal hormones (PRL: 15 min; TSH: 30 min; FSH: 30 min; LH: 30 min). In order to investigate a possible direct action of hypothalamic hormones on immune cells, we also evaluated, in the same subjects, the influence of LHRH and TRH on IFN-gamma production by human peripheral blood mononuclear cells (PBMCs), collected before the intravenous administration of the peptides and stimulated in vitro with bacterial superantigen staphylococcal enterotoxin A (SEA) and concanavalin A (Con A). LHRH and TRH, separately and together, significantly enhanced in vitro IFN-gamma production by SEA- and ConA-activated PBMCs. The present results suggest that hypothalamic peptides (LHRH and TRH) directly, and/or indirectly pituitary hormones (PRL, TSH, FSH, and LH) or IL-2, have stimulatory effect on IFN-gamma producing cells and are further evidence of interactions between the neuroendocrine and immune systems.     

Reproductive hormone profile among pesticide factory workers

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, as well as urinary levels of FSH, LH, and E1C, a metabolite of testosterone, were measured to investigate the adverse reproductive effects of organophosphate pesticides among Chinese factory workers who were occupationally exposed to ethylparathion and methamidophos. Thirty-four exposed workers were randomly chosen and recruited from a large pesticide factory, and 44 unexposed workers were selected from a nearby textile factory. A quantitative pesticide exposure assessment was performed among a subset of the exposed and unexposed workers. Information on potential confounders was collected in an interview. A single blood sample was collected at the end of a work shift, when each subject also donated a semen sample. Three first-voided urine samples were collected from each worker on 3 consecutive days. Urinary p-nitrophenol level at 1 hour after the work shift correlated with serum (r = 0.71, P < 0.01) and urinary (r = 0.51, P = 0.04) FSH levels. Stratifying by the subjects' exposure status, we found a significant negative correlation among the exposed group between urinary FSH level and sperm count (r = -0.61, P < 0.01) and between urinary FSH level and sperm concentration (r = -0.53, P = 0.03). Pesticide exposure alone was significantly associated with serum LH level (beta [coefficient of exposure effect] = 0.79; 95% confidence interval [CI] = 0.42, 1.16) but not with serum FSH or testosterone or with any urinary hormone levels. With adjustment for age, rotating shift work, current cigarette smoking, and current alcohol consumption, exposure significantly increased the serum LH level by 1.1 mIU/mL (95% CI = 0.34, 1.82). Meanwhile, the serum FSH level was slightly elevated (beta [coefficient of exposure effect] = 1.38; 95% CI = -0.09, 2.85) and the serum testosterone level was decreased (beta = -55.13; 95% CI = -147.24, 37) with increased pesticide exposure. Age and rotating shift work appeared to act as confounders. We conclude that organophosphate pesticides have a small effect on male reproductive hormones, suggestive of a secondary hormonal disturbance after testicular damage.     

Suckling-induced inhibition of luteinizing hormone secretion and follicular development in the early postpartum sow

The endocrine basis of lactational anestrus, the causes of reproductive dysfunction after early weaning, and the relationships among LH, FSH, and prolactin (PRL) secretion and follicular development were evaluated in sows weaned 6 h after farrowing (zero-weaned, n = 8) and in normally lactating sows (n = 9). An irregular, high-frequency episodic-type pattern of LH secretion was present in the early postpartum period, irrespective of treatment, and in a proportion of sows this pattern was associated with a marked elevation of baseline LH concentrations. This pattern of LH secretion was maintained in the zero-weaned sows but LH secretion was inhibited in lactating sows, resulting in a difference (p < 0.05) in mean plasma LH between groups 72-78 h postpartum. There were no differences in FSH between groups in any period of sampling. Variable but elevated plasma PRL was observed in suckled sows but declined (p < 0.05) to basal levels within 12 h of zero-weaning. Follicular development measured at laparotomy or slaughter 96 h postpartum was greater (p < 0.05) in zero-weaned than in control sows. The development of lactational anestrus in the sow therefore requires suckling-induced inhibition of LH secretion by 78 h postpartum. This inhibition of LH release does not appear to be causally related to short-term changes in PRL secretion.     

Follicle-stimulating hormone, human chorionic gonadotropin, and prolactin receptors in hamster corpora lutea or dispersed luteal cells during pregnancy

In vitro progesterone (P4) production by hamster luteal cells is stimulated throughout pregnancy by FSH and LH. Prolactin (PRL) by itself, however, increases P4 synthesis only on Day 12; on Day 4, FSH+LH+PRL induces optimal P4 secretion [Biol Reprod 1994; 51:43-49]. In light of these findings, in this study we investigated FSH, hCG, and PRL receptors in hamster CL or dispersed luteal cells on Days 4, 8, and 12 of pregnancy. Scatchard analysis of hamster CL on Days 4 and 8 showed considerably more unoccupied hCG receptors than FSH receptors: on Day 4, there was 9.5 fmol/mg protein for FSH binding sites vs. 1741 fmol/mg protein for hCG binding. Moreover, the binding affinity of hCG was greater than for FSH: the Day 4 Kd was 0.136 nM for hCG vs. 0.308 for FSH. Similar differences were observed on Day 8. Dispersed luteal cells (large+small cells) were incubated for 24 h with or without 10 ng of ovine FSH, LH, and PRL or human recombinant FSH (r-hFSH), alone or in different combinations. The cells were then washed and incubated for 4 h with iodinated hCG, FSH, or PRL with or without 100-fold excess of unlabeled hormones. The number of binding sites per 200,000 luteal cells did not change appreciably for FSH and hCG on Days 4 and 12 of pregnancy, whereas PRL binding sites significantly increased on Day 12.(ABSTRACT TRUNCATED AT 250 WORDS)     

Conjugated equine estrogens alone, but not in combination with medroxyprogesterone acetate, inhibit aortic connective tissue remodeling after plasma lipid lowering in female monkeys

The objective of this study was to determine the arterial responses to plasma lipid lowering alone or in combination with (1) estrogen replacement therapy or (2) hormone replacement therapy in surgically postmenopausal female monkeys with preexisting atherosclerosis. Eighty-eight female cynomolgus macaques were ovariectomized, fed an atherogenic diet for 24 months, and then assigned by randomized stratification into 4 groups. One group (baseline, n=20) was necropsied at the end of the atherogenic diet period; the remaining 3 groups were fed a plasma lipid-lowering diet (regression) for 30 months. These regression groups were control (diet only), CEE (receiving conjugated equine estrogens alone), and CEE+MPA (receiving CEE and continuous medroxyprogesterone acetate). A previous report described coronary artery functional and histological results; the present report describes biochemical and histological results from the abdominal aorta. Aortic plaque size was not different between groups, similar to previous findings in the coronary arteries. Aortic cholesterol content (milligrams per gram lipid-free dry weight) was lower in the regression groups compared with baseline, both for free cholesterol (mean, control=19.1, CEE=15.7, CEE+MPA=14.4, and baseline=32.7; P<0.001) and for esterified cholesterol (mean, control=18.9, CEE=15.4, CEE+MPA=14.2, and baseline=58.7; P<0.001). This cholesterol efflux could lead to increased plaque stability without changing the physical size of the lesion. Alterations in aortic connective tissue composition were observed in the regression groups. When expressed as a percentage of the lipid-free tissue weight, the aortic elastin content of the control (mean=14.9) and the CEE+MPA (mean=14.0) groups was lower than that of the baseline group (mean=19.0), which was not different from that of the CEE group (mean=15.8). Aortic collagen content, as estimated by hydroxyproline content per milligram of lipid-free tissue, was higher in the control group (mean=67.4) and the CEE+MPA group (mean=66.1) than in the baseline group (mean=56.2; P<0.05). Collagen content of the CEE group (mean=58.9) was not different from that of the baseline group. When the regression groups were considered separately, the aortic collagen content of the CEE group was lower than that of the control group (P<0.05) and tended to be lower than that of the CEE+MPA group (P=0.10), suggesting that CEE therapy (but not CEE+MPA) inhibits potentially detrimental connective tissue alterations that accompany lesion regression. These results have implications for combinations of lipid-lowering and hormone replacement therapies in relation to vascular remodeling and abdominal aortic aneurysm development.     

In vitro effects of CINC/gro, a member of the interleukin-8 family, on hormone secretion by rat anterior pituitary cells

We investigated the effects of CINC/gro on hormone secretion using normal rat anterior pituitary cells. In normal anterior pituitary cells, 10-100 ng/ml of CINC/gro significantly increased the secretion of PRL within 3 h of incubation, and two-fold enhancement of PRL secretion was induced by 100 ng/ml of CINC/gro within 24-h incubation, while the response of GH and ACTH secretions to CINC/gro was weak. On the other hand, CINC/gro suppressed basal LH and FSH secretions in a concentration-dependent manner. The percent inhibition of basal secretion by CINC/gro (50 ng/ml) within 24-h incubation was 70% for LH and 43% for FSH. Twenty-four-hour incubation with 100 ng/ml of IAP completely blocked the CINC/gro-stimulated PRL and GH secretions and CINC/gro's suppression of both basal LH and FSH secretions. These data demonstrate a new biological activity for CINC/gro and provide evidence for immune system regulation of anterior pituitary hormone secretion.     

Effects of hormonal replacement therapy on plasma sex hormone-binding globulin, androgen and insulin-like growth factor-1 levels in postmenopausal women

Plasma sex hormone-binding globulin (SHBG) levels are important in the regulation of plasma free and albumin-bound androgens and estrogens. In postmenopausal women associated to the decrease of estrogen production, a decrease of plasma SHBG levels occurs. Hormone replacement therapy (HRT) in postmenopausal women modulates plasma SHBG levels, in relationship with the different regimens and routes of administration. The present study aimed to compare the effect of different HRT on plasma SHBG levels in relationship with the changes of plasma androgen [dehydroepiandrosterone sulphate (DHEAS), testosterone (T), androstenedione (A)] and insulin-like growth factor-1 (IGF-1) levels. In a retrospective study 443 postmenopausal women were studied and divided into 2 groups. The group 1 (n = 170) was subdivided in 4 groups of women as follows: A) treated with transdermal 17-beta estradiol + medroxyprogesterone acetate, B) treated with oral conjugated estrogens, C) treated with sequential HRT (estradiol valerate (EV) + norgestrel), and D) treated with a combined HRT (micronized estradiol (E2) + noretisterone acetate). Women of group 2 (n = 273) did not receive HRT and served as controls. All groups of women treated with different HRT showed plasma estradiol levels significantly higher than controls (p < 0.01), showing the highest values in women treated with oral HRT. Plasma SHBG levels were not significantly different between patients treated with transdermal 17-beta estradiol + medroxyprogesterone acetate and controls. On the other hand, all the groups of patients treated with oral conjugated estrogen with or without progestagens showed plasma SHBG levels significantly higher than controls (p < 0.01). Plasma SHBG levels were higher in the group treated with estrogen alone than in groups of women treated with sequential or combined HRT. Plasma DHEAS, T and A levels in patients treated with different HRT regimens were in the same range of levels as control women. Plasma IGF-1 levels were not significantly affected by the various HRT regimens and remained in the same range as controls. In conclusion, plasma SHBG levels increase following oral HRT while are not affected by transdermal HRT. Plasma IGF-1 and androgen levels are not influenced from oral or transdermal HRT.     

Antipolymer antibody reactivity in a subset of patients with fibromyalgia correlates with severity

Postmenopausal hormone replacement therapy (HRT) has favorable effects on the serum lipid profile, and it also decreases the risk of cardiovascular diseases. The apolipoprotein E genotype has influence on serum levels of lipids and lipoproteins; apoE allele epsilon4 (apoE4) is associated with high total and LDL cholesterol levels. Genotype also influences the lipid responses to treatment with diet and statins, but the effect of HRT in different apoE genotypes is unknown. We studied the effects of HRT on the concentrations of serum lipids in apoE4-positive early postmenopausal women (genotypes 3/4 and 4/4) compared with apoE4-negative women (genotypes 2/3 and 3/3) in a population-based, prospective 5-year study. In all, 232 early postmenopausal women were randomized into 2 treatment groups: an HRT group (n=116), which received a sequential combination of 2 mg estradiol valerate (E2Val) from day 1 to 21 and 1 mg cyproterone acetate (CPA) from day 12 to 21 (Climen), and a placebo group (n=116), which received 500 mg/d calcium lactate. Serum concentrations of total, LDL, and HDL cholesterol and triglycerides were measured at baseline and after 2 and 5 years of treatment. A total of 154 women completed the final analysis. During the follow-up period, serum total cholesterol and LDL cholesterol concentrations decreased in the HRT group in apoE4-negative women (8.1% and 17.1%, respectively; P<0.001) but did not change in the HRT group in apoE4-positive women or in the placebo group. Serum HDL cholesterol concentrations decreased in the placebo group (apoE4-negative, 3.9%, P=0.015; apoE4-positive, 8.1%, P=0.004) but did not change significantly in the HRT group. Serum triglyceride levels tended to increase in both study groups and genotypes (15.1% to 36.2%, P<0.038 to 0.001), but no differences were observed between the study groups or genotypes, respectively. Our finding was that in postmenopausal Finnish women LDL cholesterol levels in apoE4-negative subjects respond more favorably to HRT than those in apoE4-positive subjects. This finding has potential importance in postmenopausal women with hypercholesterolemia, if confirmed in other studies.     

Changes in serotonin level and turnover in discrete hypothalamic nuclei after pinealectomy and melatonin administration to rats

OBJECTIVE: It has previously been shown that 17 beta-oestradiol (E2) implants counteract the formation of more acidic isoforms of the gonadotrophins in post-menopausal women. A much lesser effect was observed on the charge of the gonadotrophin isoforms in women with chronic oral daily therapy with 2 mg E2 combined with a progestogen, 1 mg norethisterone acetate (NETA), in spite of similar serum levels of E2 and SHBG. The presence of the progestogen in the latter study may explain the difference observed. The present study investigated the effect of the progestogen NETA on the charge and concentration of serum FSH and LH in E2 implant treated women. DESIGN: A group of 8 post-menopausal women, mean age 65 years (range 50-80 years) treated with 20 mg E2 implants every 6 months, participated in the study. The women were given a daily oral medication of 5 mg NETA for a 4-week period starting at 4 weeks after the insertion of an E2 implant (mean serum E2 420 pmol/l). This treatment with NETA was repeated in 6 of the women starting at 18 weeks after the insertion of the E2 implant (mean serum E2 317 pmol/l). Blood samples were obtained at the start of the NETA therapy, after 2 and 4 weeks of treatment and at 4 weeks after the last NETA treatment. The effects of NETA therapy on the charge of the serum gonadotrophin isoforms was determined by electrophoresis in 0.1% agarose suspension and FSH, LH, E2, and SHBG were determined with fluoroimmunoassays. RESULTS: The NETA treatment decreased the serum FSH and LH levels after 2 weeks to 24 and 23% of the levels before NETA and after 4 weeks to 14.6 and 8.8%, which were 1.3 and 2.2% of the mean levels for non-treated post-menopausal women. Both FSH and LH isoforms became more acidic during the first 2 weeks of treatment. During the following 2 weeks of NETA treatment the isoforms of both FSH and LH became more basic again. Ten weeks later both the concentration and the charge of the gonadotrophins were similar to those before the NETA treatment. The changes in concentration and charge of the gonadotrophins during the second treatment period were similar to those during the first. All the changes were statistically significant (P < 0.05 - < 0.001). The mean SHBG level decreased (P < 0.01) from 84.5 to 70.6 nmol/l after 2 weeks and to 59.9 nmol/l after 4 weeks of NETA treatment and increased (P < 0.01) 10 weeks later to 77 nmol/l. CONCLUSION: In the oestradiol treated women, the effect of the progestogen norethisterone acetate on the charge of the gonadotrophin isoforms was time-related. The oestradiol effect on the charge was counteracted during the first 2 weeks of progestogen treatment and more acidic isoforms appeared in the circulation. During the following 2 weeks the isoforms became more basic again. The levels of the gonadotrophins were efficiently decreased after 2 weeks of progestogen treatment and further decreased after 4 weeks. The time-related effect of the progestogen on the gonadotrophin isoforms may be mediated via changes in the pattern of GnRH release from the hypothalamus. The observed gradual decrease in the SHBG level during the progestogen therapy may cause an increased oestradiol effect on the hypothalamus and pituitary.     

Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer

Many previous studies evaluating various hormone levels in males with subnormal semen analyses were performed when the normal semen parameters were considerably higher than now. This study evaluated sera levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TET), free TET, and prolactin (PRL) in 60 males with oligospermia and decreased motility according to recent World Health Organization standards. Three separate groups were evaluated: group 1, motile density (MD) < 5 x 10(6)/mL (but not azoospermia); group 2, 5 < or = MD < 10 x 10(6)/mL; group 3, MD > 10 x 10(6)/mL, but % motility < 30%. There were no significant differences in mean FSH levels between groups. Overall FSH was increased in 47.1% of the cases. In contrast, mean LH levels were normal in all three groups. Only 17.3% of the entire group had elevated LH levels. The TET level was below normal in 32.3% of the entire group, with a fairly equal distribution between the three groups. Overall, only 7.8% had elevated PRL levels, with the highest percentage found in group 3 (22.2%). Only a small minority of patients with increased FSH had low TET levels compared to 48.0% of those with normal FSH. These data demonstrate that when using the lower semen parameters, the most common serum hormone abnormality is increased FSH; men with MD < 5 x 10(6)/mL do not have a higher incidence of elevated FSH than those with higher MDs.(ABSTRACT TRUNCATED AT 250 WORDS)